The goal of this research project is to identify non-coding functional elements that may influence type 2 diabetes (T2D)-related genes, and pinpoint DNA variants that perturb their regulatory function and increase T2D susceptibility. The location of T2D-associated genomic loci suggests that disease susceptibility is influenced by variants in non-coding regulatory regions. Insulin resistance in peripheral tissues like adipose and muscle, and pancreatic islet beta-cell dysfunction, are hallmarks of T2D. Accordingly, the research in this proposal will involve all three of these human tissue types. Although T2D has been researched extensively at the basic and clinical level, the high-throughput genomics experiments proposed here are only recently possible. This project uses genome-wide profiling technologies: genotypes, epigenomics, and transcriptomics to understand how regulatory variations control genes in T2D. Completion of this research will provide a high-resolution genome-wide map of T2D relevant regulatory regions, their functional impact on gene regulation, and correlations with clinical phenotypes.